ACE2 Function: Renin-Angiotensin System
The attachment and entry of coronaviruses is dependent on spike protein-receptor specificity. Angiotensin Converting Enzyme 2 (ACE2)—a transmembrane protein found on the plasma membrane of cells in lungs, vascular endothelium, kidneys, etc—is the receptor for SARS-COV2.
ACE2 is a key component of the Renin-Angiotensin System (RAS) that regulates blood pressure, fluid and electrolyte balance. When the renal blood flow is reduced (e.g. dehydration), the juxtaglomerular cells in the kidney release renin. Renin in turn activates the hormone angiotensinogen (synthesized in the liver) to angiotensin I which is subsequently activated to angiotensin II by Angiotensin Converting Enzyme (ACE).
Angiotensin II is a potent vasoconstrictor (increases blood pressure) and stimulates the release of vassopressin thus increasing water reabsorption. It also stimulates the release of aldosterone from the adrenal cortex, a hormone that increases reabsorption of water and sodium ions (Na+).
Angiotensin Converting Enzyme 2 (ACE2), a homologue of ACE, shuts down the RAS by catalyzing the cleavage of Angiotensin II into Ang(1-7). Ang (1-7) are vasodilatory peptides that counter the action of Angiotensin II. They are also anti-inflammatory and anti-fibrotic, preventing organ damage caused by overactivation of RAS.
SARS-CoV-2 and ACE2
ACE2 is found in many cell types and tissues including the lungs, kidneys, heart, blood vessels, liver and gastrointestinal tract. It is also present in epithelial cells.
The binding of the virus to its host cell receptor, ACE2, reduces its expression. This means that angiotensin II will persist even in the absence of a stimulus leading conditions such as acute lung failure. This is especially critical in hypertensive, diabetic and coronary heart disease patients whose blood pressure need constant monitoring.
Serum levels of angiotensin II have been found to be elevated in COVID19 patients, providing evidence of the role of activation of RAS and concurrent down-regulation of ACE2 in the pathology of lung injury after SARS-CoV2 infection.
Therapeutic Approach
One of the proposed therapeutic approaches is the use of a recombinant human ACE2 protein (rhACE2) that competitively binds SARS-CoV2. This is aimed at reducing blood pressure and organ injury caused by hypertension.